Kimberly Merani (Kitsis Lab): "The role of CMA in the differentiation of cardiac fibroblasts to myofibroblasts"

Dr. Toshiro Saito (Sadoshima Lab) recently competed as one of five finalists for the AHA's prestigious Louis N. and Arnold M. Katz Prize for Young Investigators.

Dr. Julio Madrigal-Matute and Bianca Sander, September 2016

Dr. Elke Marsch and Dr. Julio Madrigal-Matute, August 2016

Recently, the research group of Prof. Ana Maria Cuervo demonstrated that chaperone-mediated autophagy (CMA) is an important regulator of lipid metabolism (Schneider, Suh et al. 2014, Kaushik and Cuervo 2015). Likewise, studies by Dr. Judith Sluimer´s group showed that loss of prolyl hydroxylase (PHD) 1 (Marsch, Demandt et al. 2016) and PHD2 reduces cholesterol levels and alleviates atherosclerotic burden. Presence of a CMA targeting motif in the PHD amino acid sequence, as well as the long half-life of PHD proteins make them a likely target for CMA. We hypothesize that CMA might regulate cholesterol levels, in part through regulated degradation of PHD proteins. Being a member of the Leducq network has enabled an active collaboration between both groups, which has already resulted in two research exchanges of members of the Sluimer group to the Cuervo lab in 2016. Former PhD student Dr. Elke Marsch and new PhD student Bianca Sander provided hands-on help with dissection of tissues from mouse models with genetically modulated CMA and benefitted immensely from Cuervo group’s expertise in CMA. Furthermore, Bianca was able to learn important CMA-related techniques like the usage of a fluorescent CMA reporter assay to monitor this pathway. She performed immunoblot and immunofluorescence analyses of autophagy-related proteins on atherosclerosis samples and is now able to establish those techniques in the Sluimer lab. These short-term exchanges were important to align techniques for atherosclerosis and CMA in both groups. As the project evolves, we anticipate that additional exchanges in between the groups might be required in the future to further implement and standardized methodology and to accelerate data acquisition in this project. The collaboration between Cuervo and Sluimer labs has already generated exciting preliminary data in support of the interplay between CMA and PHDs in cholesterol metabolism and atherosclerosis, which was the basis of the successful acquisition of a prestigious Dr. Dekker career grant from the Dutch Heart Foundation Dekker for Dr. Judith Sluimer.